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Dev Mittar, Ph.D., Scientific Director of the ASM Health Scientific Unit discusses the use of metagenomic next generation sequencing to develop agnostic diagnostic technology, giving scientists and clinicians alike, a tool to diagnose any infectious disease with one single test. He also discusses how the ASM Health Unit is empowering scientists and leveraging microbial science innovations to address critical global health challenges and improve lives worldwide.
Ashley's Biggest Takeaways The Division of Research, Innovation and Ventures is a small entrepreneurial arm of BARDA that takes on early-stage projects with high potential of turning into medical countermeasures. Prior to his role as Scientific Director for ASM Health, Mittar worked as a health scientist and program officer at DRIVe, where he focused on advancing high-impact science. He is particularly passionate about his work to develop agnostic diagnostics—a single test that uses metagenomic next generation sequencing to identify any pathogen from 1 clinical sample. Mittar discusses applications for this technology in surveillance (pandemic preparedness), variant detection, AMR and clinical settings (diagnosing complicated infections where etiology is not clearly defined). He also shares how a recent bout with illness emphasized the value and potential of this technology to save money, time, pain and suffering of the patient. Agnostic diagnostics can also help prevent the overuse/misuse of antibiotics, which are key factors in the spread of antimicrobial resistance. Furthermore, when this technology is coupled with the use of metatranscriptomics, it can provide information about the patient’s immune profile that can be helpful in developing personalized treatment strategies, as opposed to a one-size-fits-all approach. ASM is organizing around 3 scientific units, ASM Health, ASM Mechanism Discovery and ASM Applied and Environmental Microbiology. These units will empower researchers and scientists to use science make a difference in the world and provide a forum for them to come together to shape the future of the field. Links for This Episode Learn More About ASM’s Scientific Units. Join the Conversation on ASM Connect, our online community platform. Browse Volunteer Opportunities. Become an ASM Member. Register for ASM Microbe 2025. -
Episode Summary Afreenish Amir, Ph.D., Antimicrobial Resistance (AMR) Project Director at the National Institute of Health in Pakistan, highlights significant increases in extensively drug-resistant typhoid and cholera cases in Pakistan and discusses local factors driving AMR in Asia. She describes the development and implementation of a National Action Plan to combat AMR in a developing country, emphasizing the importance of rational antimicrobial use, surveillance and infection control practice. Ashley's Biggest Takeaways AMR is a global and One Health issue. Pakistan has a huge disease burden of AMR. Contributing factors include, but are not limited to, overcrowding, lack of infection control practices, poor waste management practices and over-the-counter prescription practices. Promoting the rational use of antimicrobials is imperative at all levels—from tertiary care to primary care practitioners. Typhoid and cholera are high-burden infections in Pakistan, with typhoid being a year-round issue and cholera being seasonal. A holistic approach, involving various sectors and disciplines, is necessary in order to address the global AMR threat. Amir highlights the need for better communication and collaboration to bridge gaps and build trust between different organizations. Featured Quotes: I've been working at the National Institutes of Health for the last 7 years now. So, I've been engaged in the development and the implementation of the national action plan on AMR, and that gave me the opportunity to explore the work in the field of antimicrobial resistance. Reality of AMR in Pakistan [Pakistan] is an LMIC, and we have a huge disease burden of antimicrobial resistance in the country right now. A few years back, there was a situational analysis conducted, and that has shown that there is presence of a large number of resistant pathogens within the country. And National Institutes of Health, they have started a very standardized surveillance program based upon the global antimicrobial use and surveillance system back in 2017. And [those datasets have] generated good evidence about the basic statistics of AMR within the country.
So, for example, if I talk about the extensively drug-resistant typhoid, typhoid is very much prevalent in the country. Our data shows that in 2017 there were 18% MDR typhoid cases through the surveillance data. And in 2021 it was like 60%. So that has shown that how the resistance has increased a lot. A number of challenges are associated with this kind of a thing, overcrowded hospitals, poor infection prevention and control (IPC) measures. So, there is AMR within the country—there's a huge burden—and we are trying to look for the better solutions. Local Factors Driving AMR Bacteria, they do not know the borders. We have a close connection with the other Asian countries, and we have a long border connected with the 2 big countries, which are Afghanistan and India and Bangladesh and China. So, we see that it's not limited to 1 area. It's not regional.
It’s also a history of travel. When the people travel from one area to the other, they carry the pathogen as a colonizer or as a carrier, and they can infect [other] people. So, it's really connected, and it's really alarming as well.
You never know how the disease is transmitted, and we have the biggest example of COVID—how things have spread from 1 country to the other, and how it has resulted in a massive pandemic. AMR is similar. We have seen that it's not limited to 1 region. We are part of this global community, and we are contributing somehow to the problem.
First, I'll talk about the health care infrastructure. We do have the capacities in the hospitals, but still, there's a huge population. Pakistan is a thickly populated country. It's a population of around 241 million. And with the increasing population, we see that the infrastructure has not developed this much. So now the existing hospitals are overcrowded, and this has led to poor infection control practices within the hospitals. The staff is not there. In fact, ID consultants are not available in all the hospitals. Infection control nurses are not available in all the hospitals. So, this is one of the main areas that we see, that there is a big challenge.
The other thing that can contribute is the poor waste management practices. Some of the hospitals—private and public sectors—they are following the waste management guidelines—even the laboratories. But many of the hospitals are not following the guidelines. And you know that AMR is under one health. So, whatever waste comes from the hospital eventually goes to the environment, and then from there to the animal sector and to the human sector.
[Another big] problem that we are seeing is the over-the-counter prescription of antimicrobials. There is no regulation available in the country right now to control the over-the-counter prescription of antibiotics. They are easily available. People are taking the antibiotics without a prescription from the doctors, and the pharmacist is giving the patients any kind of medicine. And either it is effective/not effective, it's a falsified, low-quality antibiotic for how long in duration antibiotic should be taken. So, there are multiple of things or reasons that we see behind this issue of AMR. Rational Use of Antimicrobials It is a complex process how we manage this thing, but what we are closely looking at in the country right now is that we promote the rational use of antimicrobials at all levels—not only at the tertiary care levels, but also at the general practitioner level. They are the first point of contact for the patients, with the doctors, with the clinicians. So, at this point, I think the empirical treatment needs to be defined, and they need to understand the importance of this, their local antibiograms, what are the local trends? What are the patterns? And they need to prescribe according to those patterns.
And very recently, the AWaRE classification of WHO, that is a big, big support in identifying the rational use of antimicrobials—Access, Watch and Reserve list—that should be propagated and that should be understood by all the general practitioners. And again, I must say that it's all connected with the regulations. There should be close monitoring of all the antibiotic prescriptions, and that can help to control the issue of AMR. National Action Plan on AMR So, when I joined NIH, the National Election plan had already been developed. It was back in 2017, and we have a good senior hierarchy who has been working on it very closely for a long period of time.
So, the Global Action Plan on AMR, that has been our guiding document for the development of the national action plan on AMR, and we are following the 5 strategic objectives proposed in the global action plan. The five areas included: The promotion of advocacy and awareness in the community and health care professionals. To generate evidence through the data, through the surveillance systems. Generation of support toward infection prevention and control services IPC. Promoting the use of antimicrobials both in the human sector and the animal sector, but under the concept of stewardship, antimicrobial consumption and utilization. Invest in the research and vaccine and development. So, these are some of the guiding principles for us to develop the National Action Plan, and it has already been developed. And it's a very comprehensive approach, I must say. And our institute has started working on it, basically towards recreating awareness and advocacy. And we have been successful in creating advocacy and awareness at a mass level. Surveillance We have a network of Sentinel surveillance laboratories engaged with us, and they are sharing the data with NIH on a regular basis, and this is helping NIH to understand the basic trends on AMR and what is happening. And eventually we plan to go towards this case-based surveillance as well, but this is definitely going to take some time because to make people understand the importance of surveillance, this is the first thing. And very recently, the Institute and country has started working towards the hospital acquired infection surveillance as well. So, this is a much-needed approach, because the lab and the hospital go hand in hand, like whatever is happening in the lab, they eventually reach the patients who are in the hospitals.
Wastewater surveillance is the key. You are very right. Our institute has done some of the work toward typhoid and cholera wastewater surveillance, and we were trying to identify the sources where we are getting these kinds of pathogens. These are all enteric pathogens. They are the key source for the infection. And for the wastewater surveillance mechanism, we can say that we have to engage multiple stakeholders in this development process. It's not only the laboratory people at NIH, but we need to have a good epidemiologist. We need to have all the water agencies, like the public health engineering departments, the PCRWR, the environmental protection agencies who are working with all these wastewater sites. So, we need to connect with them to make a good platform and to make this program in a more robust fashion. Pathogens and Disease Burdon For cholera and typhoid within Pakistan, I must say these are the high burden infections or diseases that we are seeing. For typhoid, the burden is quite high. We have seen a transition from the multidrug-resistant pathogens to the extensively drug-resistant pathogens, which now we are left with only azithromycin and the carbapenems. So, the burden is high. And when we talk about cholera, it is present in the country, but many of the times it is seasonal. It comes in during the time of the small zone rains and during the time of floods. So, every year, during this time, there are certain outbreaks that we have seen in different areas of the country. So, both diseases are there, but typhoid is like all year long—we see number of cases coming up—and for cholera, it's mainly seasonal. Capacity Building and ASM's Global Public Health ProgramsCapacity building is a key to everything, I must say, [whether] you talk about the training or development of materials.
Links for This Episode: Experts Discuss One Health in Pakistan: Biosafety Education Inside and Outside the Lab.
I've been engaged with ASM for quite some time. I worked to develop a [One Health] poster in the local language to create awareness about zoonotic diseases. So, we have targeted the 6 zoonotic diseases, including the anthrax, including the Crimean-Congo hemorrhagic fever and influenza. And we have generated a very user-friendly kind of layout in the local language, trying to teach people about the source of transmission. What are the routes of transmission, if we talk about the CCHF? And then how this can be prevented. So, this was one approach.
And then I was engaged with the development of the Learnamr.com. This is online platform with 15 different e-modules within it, and we have covered different aspects—talking about the basic bacteriology toward the advanced, standardized methods, and we have talked about the national and global strategies [to combat] AMR, One Health aspects of AMR, vaccines. So, it's a huge platform, and I'm really thankful to ASM for supporting the program for development. And it's an online module. I have seen that there are around more than 500 subscribers to this program right now, and people are learning, and they are giving good feedback to the program as well. We keep on improving ourselves, but the good thing is that people are learning, and they are able to understand the basic concepts on AMR.Explore ASM’s Global Public Health Programs.
Download poster about zoonotic disease in English or Urdu.
Progress on the national action plan of Pakistan on antimicrobial resistance (AMR): A narrative review and the implications.
Global diversity and antimicrobial resistance of typhoid fever pathogens: insights from 13,000 Salmonella Typhi genomes.
Wastewater based environmental surveillance of toxigenic Vibrio cholerae in Pakistan.
Point Prevalence Survey of Antimicrobial Use in Selected Tertiary Care Hospitals of Pakistan Using WHO Methodology: Results and Inferences.
Overcoming the challenges of antimicrobial resistance in developing countries.
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Manuel Martinez Garcia, Ph.D., a professor of microbiology in the Physiology, Genetics and Microbiology Department at the University of Alicante in Spain, paints a picture of what microbial life looked like thousands of years ago by analyzing microbial genomic signatures within ice cores collected from the Antarctic ice shelves in the 1990s.
Links for the Episode New avenues for potentially seeking microbial responses to climate change beneath Antarctic ice shelves – mSphere paper. Viruses under the Antarctic Ice Shelf are active and potentially involved in global nutrient cycles – Nature communications article. Manuel Martinez Garcia’s Lab website. How stable is the West Antarctic Ice Shelf? – Press Release from Alfred Wegener Institute. Take the MTM listener survey! Watch this episode: https://youtu.be/CHCMO74_gIY Ashley’s Biggest Takeaways There is a unique habitat beneath Antarctic ice shelves, where microbes live without light and rely on unusual energy sources. Ice cores from these Antarctic ice shelves can preserve fossilized genomic records of microbial life from long ago. Comparing past and present samples can help us understand how microbial life is responding to environmental stressors, like temperature changes and acidification, over time. It can also provide key insights to changes in biodiversity. Featured Quotes: Motivation for the ResearchIce shelves are like massive floating ice that are in Antarctica, mainly. They can be as big as, for example, France, the country. So, they are super big—they are enormous. And they can be as thick as, let's say, 1000 meters. So, this is a massive [piece of] ice that we have in our planet.
And beneath that massive ice, we can have a very peculiar and a special habitat in which microbes live without light. They have to manage, to thrive and reproduce, without using a standard energy like we have on the surface of the sea or in the forest, where we have light that is driving and providing the energy for the ecosystem. But in this case, these ecosystems are totally different.
[The ice shelves] are deep and interconnected. Basically, there are different oceanic currents, for example, there is one Circumpolar Current that surrounds Antarctica, and there are also other currents that basically go from the bottom to the surface, moving, you know, all the water masses.
The interesting part of this story is that every single second in our lives, this sea that is beneath the platform, the ice shelf, is frozen over and over, and then we have different layers of antiquity that preserve the microbes that are living in the ocean. So, for example, let's say, 1000 years ago, the sea water was frozen, and then we can find a layer beneath the Antarctica ice shelf, where these microbes are preserved and frozen. Basically, it's like a record—a library of microbes, fossil records of microbes—from the past ocean, from 1000 years ago until present, more or less.
And then we can go to these records, to these layers of frozen sea water, and pick these samples to somehow recover the genetic material of the microbes that were preserved and frozen 1000 years ago or 500 years ago, in the way that we can somehow reconstruct or build the genetic story of the microbes from the past, for example, pre-industrial revolution to present.
We need to think that microbes sustain the rest of the food web. So, they sustain of the rest of life in the ocean. They provide carbon for the rest of organisms, the fishes, whales [and other] big animals that we have in our oceans. And if the microbes are responding in a way that is not satisfactory, or in the way that we think can maintain the food web, this is kind of scary. And this is what we are trying to do: we are trying to go back to the past and see how the microbes are changing [genetically].
Sample CollectionWe didn't collect the samples. [They were collected] back in the 90s, so, 40 years ago, by a German group led by the Alfred Wegener Institute, which is probably one of the most famous polar institutes in the world. They, basically, led an expedition, I think it was in 92, and they decided to go to this ice shelf in Antarctica, in the Filchner–Ronne Ice Shelf to collect these ice cores.
And then the surprise was when they were progressing in the drilling, they realized that on the top part of the ice core was fresh water, meteoric snow that was compacted forming the ice. But they realized that below that part, there was a sea water that was frozen. And then they thought that these samples were very interesting, because they somehow store material from the past, and they shipped these samples to Alfred Werner Institute in Bremerhaven in Germany.
And half of the samples were stored for 40 years until I decided to contact the Institute and to propose this research. And I basically contacted the director of the Institute, and also the group of Frank Wilhelm, to propose the idea. And basically, I said, ‘Hey, I think what you have in your research is a valuable material that that can provide interesting answers for climate change and microbiology.’ And they say, ‘Well, that's interesting. And we never thought about that.’ And then we started a collaboration to dig into these questions.
Shipping the Ice CoresWe had a meeting after one of the first pandemic lockdowns, when they allow [me] to travel. I went to Bremerhaven to have a personal meeting with the team. And we decided to ship some samples to Spain.
They arrived frozen and very well packaged and preserved in an isolated container. But it was really surprising to see that that they were delivered in the same compartment with a dry ham. That was a that was a funny story!
Sample PreparationWhen we received the samples, the first thing was to basically decontaminate the surface of the [ice]. Because when you unpackage, you have an ice core, pieces like a half meter. And then, we have to think that this ice core has been manipulated by different groups, different people. And you have to decontaminate the surface of the ice core in order to just have the center of the ice core for the for the investigation.
And basically, we adapted a protocol in order to make sure that we didn’t have cross contamination from the rest of the from the surface.
So, what we did was we melted the center of the core—well, in fact, different parts of the core with different ages, from 1000 years old to 200 years old—and we melted in a very dedicated laminar flow hood that we have in a clean room. And then, we extracted the DNA from that piece. And in our case, the amount of DNA was so little that we had to amplify with some molecular techniques in order to have [enough] copies of this genetic material to do sequencing.
Sample AnalysisI will say that we are in the middle of the project. We had, like, 2 years ongoing for the project.
The most surprising was 2 things. One, in the sea water, beneath the Antarctic, we discovered a very autoctonos (indigenous) viral community that was quite different from the rest of the world, I will say, from the rest of the ocean. So, I think this viral community is quite adapted to infect the microbes that are living in this peculiar environment beneath the Antarctica ice shelf.
And these viruses were carrying some genes that we think are very important for microbes. We call these genes auxiliary metabolic genes. And these genes are very important because somehow the viruses provide these pieces of information, of DNA material, to microbes that are driving important ecological roles, like, for example, carbon fixation.
It's very important, because carbon fixation is probably the primary step in all ecosystems—to provide food for the rest of the organisms. And if this is altering, or we are altering it with different factors—like temperature increase, like melting of the ice—its going to change these patterns and the rate of carbon fixation. This is going to produce a deep impact for the rest of organisms.
We are still investigating, but we think that it's interesting to think that microbes that live in our ocean now are responding to stressing factors like increasing temperature and also acidification by different ways. In fact, it is unclear—it is a very hot topic and a very hot question—because we don't know for sure what the fate of these microbes in our oceans is going to be. For example, people think that we are going to lose biodiversity. There are some hypotheses that say that heterotrophy is going to be more predominant in the sea water. But it's unclear, because we don't really have fossil records that can compare the past to the present, and this is what we can provide, or at least potentially provide. We can say, ‘Hey, we can go before the industrial revolution, before the CO2 increase, and try to compare series of different samples until the present in order to see if, for example, heterotrophy, or microbes that are heterotrophs, are more predominant in modern samples compared to unseen samples.
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Episode Summary Mother-Son duo, Brenda Wilson, Ph.D., professor of microbiology and the Associate Director of Undergraduate Education in the School of Molecular and Cellular Biology at the University of Illinois at Urbana Champaign and Brian Ho, Ph.D., researcher and lecturer at the Institute of structural and molecular biology, a joint institute between the Department of structural and molecular biology at the University College of London and the Department of Biological Sciences at Birkbeck University of London discuss the inspiration and motivation for their recent book, Revenge of the Microbes: How Bacterial Resistance is Undermining the Antibiotic Miracle, 2nd Edition, emphasizing the global nature of AMR and providing a unique perspective on what is needed to solve it. Ashley’s Biggest Takeaways: Dynamics surrounding the AMR crisis are complex and require an understanding of many different perspectives, including those of the farmers, health care professionals, pharmaceutical companies and individuals, in order to foster true and lasting global collaboration on the issue. Point-of-care diagnostics are critical to improving treatment decisions and reducing hospital costs. Better communication and education are needed in order to rebuild trust in scientists and institutions. Continuous research is necessary, as AMR will continue to evolve. Citizens are a key piece of the puzzle when it comes to pushing for change and supporting solutions to AMR. Featured Quotes:
Wilson: “I'll start with actually my Ph.D., which is talking about bacterial antibiotic biosynthesis. And so, I did some work in that arena, but since then, I've actually been working on bacterial protein toxins. These are very potent eukaryotic modulators that when bacteria get into the host, they release these proteins that are very large, that are able to interact with very specific cells. They actually get inside the cells—into the cytosol—and then they affect various signaling pathways in the host that can go anywhere from killing the cell to modulating some of the processes that the cell undertakes, even differentiating them and causing cancer.
Links for the Episode: The 2nd Edition of Revenge of the Microbes, details the intricacies of the antibiotic-microbe arms race. Beginning with a historical perspective on antibiotics and their profound impact on both modern medicine and present-day society. It also examines the practices and policies driving the discovery and development of new antibiotics, what happens to antibiotics once they are released into the environment, how antibiotic-resistant bacteria evolve and spread and the urgency for finding alternative approaches to combating infections. For anyone interested in antimicrobial resistance (AMR), this is a completely approachable 360-degree view of a very complex topic. Get your copy of Revenge of the Microbes today! Want to get involved and spread the word about AMR? Become an ASM Advocate Bacterial Pathogenesis: a Molecular Approach Take the MTM listener survey!
So, one of my main focuses in my lab has always been to understand the structure and function of these toxins, to understand how they affect the eukaryotic cell system. And then now that we know a lot about them, we're actually moving more into the direction of trying to basically use them as biologics. We have some platforms that we call bacterial toxin inspired drug delivery, where we're using the mechanisms of how they work and their exquisite specificities to be able to actually use them for therapeutic applications.”
Ho: “I got my start doing molecular genetics, actually, with John Mekalanos at Harvard, and I was kind of at the ground floor of the seminal work looking at the Type VI secretion system. And so, I got a front row seat to the kind of discovery and a lot of the initial understanding of the system. And I've kind of taken that work and expanded beyond it to look at kind of the ways different bacteria interact with each other within microbial communities. So my current work is looking at both DNA conjugation as well as the type six antagonism, and how the bacterial interactions kind of work together to build a larger population dynamics and interface with like the hosts that kind of house a your microbial communities.”
Antimicrobial Resistance
Wilson: “In 2005 [when the first edition of Revenge of the Microbes was written], there was very little activity or understanding about antibiotic resistance and how important it was. Outside of the field, doctors were encountering it. But oftentimes what was happening is they just said, ‘Oh, well, we'll just find another drug, you know.’ And pharmaceutical companies, they were recognizing that there was a problem, and they would go off trying to hunt for new ones. And then right around the late 90s, there was a big impetus, because they thought, ‘Oh, we, we have a miracle here, because we now do complete genomes. We can get out the comparative genomics and all the high throughput things, all the animations,’ and that this would lead to many more new discoveries. And I think the pharmaceutical companies were very disappointed, and they started backing out of what they deemed a huge commitment.
Two decades later, people already were starting to get aware, at least in the field, and even the industry and the physicians. People were getting aware, but I think that they were stumbling, because of their silos, in trying to get interactions with each other. And I think part of it was that they felt that, ‘Oh, we can try to solve it ourselves.’ And in reality, this is a problem that that is concerning everyone, and everyone is contributing to it. Everyone has to find a solution to help, and we need to have more synergy. There have to be more interactions, and we have to do this at a much more global scale. And so that was sort of what, what we thought when we first started the [2nd edition of the book, Revenge of the Microbes].”
Ho: “At that point, I was just starting my new faculty position, and so I started having to teach students directly. And a lot of students were coming in and giving their presentation on their research proposal or project that they have, and they very adamantly declared the reason why we have antibiotic resistance. ‘The problem is because doctors are over prescribing antibiotics.’ And I'm scratching my head—a little like, ‘Hmm, that's a really confident statement that you're making.’ Next student comes in and they're talking about, ‘Oh, it's all the farmers that are overusing antibiotics and causing the problem.’ And then the next student comes in like, “Oh, the greedy corporations or pharmaceutical industry is trying to milk us for everything, and antibiotics are not profitable enough.’ And, and I'm sitting here listening to the students who have a very narrow perspective. And clearly, they're getting it from whoever is teaching their classes.
And so, it feels like every single perspective at every single stage, they only see things through their own eyes, and can't understand what the broader perspective is and why you have all these various different problems, and I guess we call them stakeholders in the thing. It is that that every different angle has its own personal motivations. Corporations do need to have money and persist to exist. Doctors, if you encounter a patient that is dying, well, you have a moral compulsion to actually treat them. And farmers having their livestock, well, their livelihood is at stake if they don't have their animals survive, right?
And so, what I think was really important that we wanted to do is present the problem of antibiotic resistance and the way it works and why it's an issue, but also convey different perspectives on it, so that if people can kind of understand where everybody else is coming from, we can come together and have a more unified perspective, or understanding, at least, so that you're not thinking that everybody is this malicious actor, and you can actually work together to come with up with a complete solution.”
Wilson: “The first book, was very important, because you needed to get people's attention right, right? But we got the attention. So, now let's come up with a plan! And we don't have a good plan. People are making progress. People are moving in the directions that need to be moved, coming up with alternatives, coming up with, you know, even financial solutions, to some extent.
They're not enough, still, and it's going to take a global community to come forward and buy in to the problem. And I think we still have a large sector of our whole global community that are not really fully aware of what really this problem entails. They hear on the media and the news, ‘Oh, the crisis is here. We're in danger.’ And then a year later, they say, ‘Well, what happened? Nothing's happened.’ It hasn't impacted their lives yet, right? Or at least not in a way that they've noticed. And I think this is why we need more awareness. We need to get the word out there. We need to actually start having folks that make some of the big decisions, both financially, regulatory and other types of things, like education.”
Ho: “One really big problem I think that COVID introduced us to, is that it's not just that we have to convince everybody it's important, but we have to also get people, in general, the population, to trust us. You know, that there is a problem. There's been a kind of an erosion in the trustworthiness, or trust in the institutions that we relied upon that are responsible for keeping everybody safe and healthy. And I think a big part of that is also communication education, that the populace needs to be better educated, but the communication level of people in charge, as well as researchers like us—we need to speak to the people in a way that people can understand.”
Wilson: “We're not saying that we have a solution, but we do have some directions that, in many areas, have started, and we feel that they need more support. And we're hoping that folks that are reading the book actually appreciate that aspect of it, and then start realizing that, ‘Hey, I'm part of this solution too.’ It can be very little—being mindful of making sure that we have clean water, making sure that we have food security, making sure that we stay healthy and, therefore, we don't have as many infections, right? Just little things like that that we can actually do as individuals, that as a whole population, will actually contribute to improving the situation.
Then, of course, we have to support our leaders in making some of the decisions. We have to let them know that we care about this. And I think at this stage, what we're hoping is that we can maybe encourage some folks to take a citizen stand on this, to ask questions, to start going and probing and saying, ‘Hey, congress person, what are you doing about this?’ And maybe just start the dialog. This is all we're doing, is starting a dialog.” -
Joseph James, biologist at the U.S. Environmental Protection Agency, discusses his career trajectory and the creation of Binning Singletons, a unique mentorship program built on peer-to-peer networking at scientific meetings and conferences and was first implemented in 2019 at ASM Microbe.
Links for the Episode Binning Singletons and Peer-to-Peer Networking Learn more about Binning Singletons. Contact Joe James: [email protected] Follow Binning Singletons on Bluesky. Binning Singletons: Mentoring through Networking at ASM Microbe 2019—mSphere article. Binning Singletons: Tackling Conference Networking When You Don’t Know Anyone—Guest post on Addgene Blog. Mastering a Mentoring Relationship as the Mentee—asm.org article that James says has really helped him explain Binning Singletons as a coaching form of mentorship. Mapping a Mentoring Roadmap and Developing a Supportive Network for Strategic Career Advancement—article on developing networks of mentors, another area Binning Singletons tries to address. #FEMSmicroBlog: Networking at Online Conferences (for Early Career Scientists). Take the MTM listener survey! James’ Research Dietary lead modulates the mouse intestinal microbiome: Subacute exposure to lead acetate and lead contaminated soil. In situ differences in nitrogen cycling related to presence of submerged aquatic vegetation in a Gulf of Mexico estuary. Quantifying stream periphyton assemblage responses to nutrient amendments with a molecular approach. Analysis of Bacterial Communities in Seagrass Bed Sediments by Double-Gradient Denaturing Gradient Gel Electrophoresis of PCR-Amplified 16S rRNA Genes. Use of composite data sets for source-tracking enterococci in the water column and shoreline interstitial waters on Pensacola Beach, Florida. -
Saeed Khan, Ph.D., Head of the Department of Molecular Pathology at Dow diagnostic research and reference laboratory and President of the Pakistan Biological Safety Association discusses the importance and challenges of biosafety/biosecurity practices on both a local and global scale. He highlights key steps for biorisk assessment and management and stresses the importance of training, timing and technology.
Ashley's Biggest Takeaways Adequate biosafety and biosecurity protocols depend on a thorough understanding of modern challenges, and scientists must be willing and able to respond to new technological threats appropriately. In the microbiology lab, the threat goes beyond the physical pathogen. Implications of genomics and cyber security must be built into biorisk management techniques, including data storage and waste management practices. Risk assessments involve evaluation of both inherent and residual risk. Inherent risk is linked to the pathogen. Residual risk varies according to the lab, equipment, employee, environment, etc. As a result, biosafety and biosecurity risks are constantly changing, and assessments must be repeated strategically and often. Khan recommended repeating a risk assessment whenever a key variable in the equation changes, i.e., new equipment, new employee, new pathogen. He also recommended (at minimum) conducting routine risk assessments every 6 months, or twice a year. Featured Quotes:“We need to have basic biosafety and biosecurity to stay away from these bugs and the modern challenges, like cyber biosecurity and genomics. These are the new areas, which are potential threats for the future, and where we need to train our researchers and students.”
Links for the Episode ASM Guidelines for Biosafety in Teaching Laboratories Pakistan Biological Safety Association Training to be a Biosafety Professional (video) Take the MTM listener survey!
“Starting from simple hand washing or hand hygiene, the basic things we use are gloves, goggles and PPE to protect the workers, the staff and the patient from getting infected from the environment, laboratory or hospitals. These are the basic things, and it's very crucial, because if one is not using gloves in the lab or not wearing the lab coat, he or she may get infected from the sample, and the patient can get infected from the physician and doctors or nurse if they are not following the basic biosafety rules. These [things] are routinely important. Every day we should practice this.”
“But there are [also] new challenges. Particularly in the microbiology lab, we [used to] think that once we killed the bacteria, then it's fine. But nowadays, it's not the way we should think about it. Though you kill the bacteria practically, it still has a sequence, [which] we call the genome, and if you have that information with you, you theoretically have the potential to recreate that pathogen… that can be used or maybe misused as well.”
“[Working with] scripts of pathogens, like smallpox or the polioviruses, we call this synthetic biology. Different scientists are doing it for the right purposes, like for production of vaccines, to find new therapeutics, to understand the pathology of the diseases. But on [the other hand]—we call it dual use research of concern (DURC)—the same can be misused as well. That's why it's very important to be aware of the bugs that we are working with, and the potential of that pathogen or microbe, to the extent that can be useful or otherwise.”
“So, we should be aware of the new concern of the technology, synthetic biology and DURC. These are new concepts—cyber, biosecurity and information security [are all] very much important these days. You cannot be relaxed being in the microbiology lab. Once we have identified a pathogen, declared a result to the patient and the physician, and it's been treated, we [still] need to be worried about waste management—that we discard that waste properly and we have proper inventory control of our culture. It should be safe in the locker or on in the freezers and properly locked, so we should not be losing any single tube of the culture, otherwise it may be misused.”
Risk Assessment
“The best word that you have used is risk assessment. So, it should gage the severity of the issue. We should not over exaggerate the risk, and we should not undermine the risk. Once the risk assessment been made, we can proceed.”
“Right from the beginning of touching a patient or a sample of the patient until the end of discarding the sample, that is called biorisk management. It's a complete science that we need to be aware of—not in bits and pieces. Rather a comprehensive approach should be adopted, and each and every person in the organization should be involved. Otherwise, we may think [we are] doing something good, but someone else may spoil the whole thing, and it will be counterproductive at the end.”
“We should involve each and every person working with us and the lab, and we should empower them. They should feel ownership that they are working with us, and they are [as] responsible as we are. So, this the whole process needs to be properly engaged. People must be engaged, and they should be empowered, and they should be responsible.”
“Each and every lab has different weaknesses and strengths of their own, which play an important role in the risk assessment.”
“There is inherent risk, which is linked with the pathogen, and there is another thing we call residual risk. So, residual risk everywhere and varies. Though the inherent risk may be the same, the residual risk is based on the training of the person, the lab facility that is available, the resources that labs have and the potential threats from the environment.”
“It's not usually possible that you do a risk assessment every day. So, when you have different factors involving a new pathogen in your lab, you have new equipment in your in your lab, or some new employee in your lab—[a new] variable factor that is involved—you should [perform] the risk assessment. Otherwise, [a routine risk assessment] should [be done] twice a year, after 6 months.”
“Training is important, and response time is very much crucial. And different technology plays a vital role, but the lack of technology should not be an excuse for not responding. There is always an alternative on the ground that you may do the risk assessment. And within the given resources and facility, we should mimic the technology and respond to any outbreaks or disease within our given resources.” -
Nicole Dubilier, Ph.D., Director and head of the Symbiosis Department at the Max Planck Institute for Marine Microbiology, has led numerous reserach cruises and expeditions around the world studying the symbiotic relationships of bacteria and marine invertebrates. She discusses how the use of various methods, including deep-sea in situ tools, molecular, 'omic' and imaging analyses, have illuminated remarkable geographic, species and habitat diversity amongst symbionts and emphasizes the importance of discovery-driven research over hypothesis-driven methods.
Watch this episode: https://www.youtube.com/watch?v=OC9vqE1visc
Ashley's Biggest Takeaways: In 1878, German surgeon, botanist and microbiologist, Heinrich Anton de Bary, first described symbiosis as the living together of two or more different organisms in close physical intimacy for a longer period of time. These relationships can be beneficial, detrimental or commensal, depending on the organisms involved. Microbial symbiosis research holds great potential to contribute to sustainable energy production and environmental health. Links for This Episode: Learn more about one of Dubilier's research vessels and see videos from the expidition. Functional diversity enables multiple symbiont strains to coexist in deep-sea mussels. Chemosynthetic symbioses: Primer. Take the MTM listener survey! -
From Bovine Spongiform Encephalopathy (BSE) to Creutzfeldt-Jakob disease (CJD), Neil Mabbott, Ph.D., has worked for nearly 2 decades on understanding the mechanisms by which prion proteins become infectious and cause neurological disease in humans and animals. He discusses the remarkable properties of prions and addresses complexities surrounding symptoms, transmission and diagnosis of prion disease.
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Episode Summary Timothy Donohue, Ph.D.—ASM Past President, University of Wisconsin Foundation Fetzer Professor of Bacteriologyand Director of the Great Lakes Bioenergy Research Center (GLBRC) calls genomics a game-changer when it comes the potential of microbes to create renewable resources and products that can sustain the environment, economy and supply chain around the world. He also shares some exciting new advances in the field and discusses ways his research team is using microorganisms as nanofactories to degrade lignocellulose and make a smorgasbord of products with high economic value.
Take the MTM listener survey! Ashley's Biggest Takeaways: The bioeconomy can be broadly defined as the use of renewable resources, including microorganisms, to produce valuable goods, products and services. Microbes have the potential to create products that cannot be made by existing synthetic chemistry routes. Using raw, renewable resources to create a circular bioeconomy is beneficial to the environmental footprint, economic footprint and supply chain security around the globe. Links for This Episode: The theme of our Spring 2024 Issue of Microcosm, our flagship member magazine is Microbes and the Bioeconomy: Greasing the Gears of Sustainability, launches this week and features an article based on this MTM conversation. If you are an ASM Member, check back on Wed., June 30 for the newly published content! Not a member? Consider renewing or signing up today, and begin exploring endless potential to boulster your career and network with professionals, like Donohue, in your field. Get Bioeconomy Policy Updates. Heading to ASM Microbe 2024? Check out this curated itinerary of sessions on the bioeconomy, including those discussing the use of algae for bioproduction and synthetic biology for natural product discovery. Learn more about the Great Lakes Bioenergy Research Center. MTM listener survey! -
Rodney Rohde, Ph.D., Regents’ Professor and Chair of the Medical Laboratory Science Program at Texas State University discusses the many variants, mammalian hosts and diverse neurological symptoms of rabies virus.
Ashley’s Biggest Takeaways: Prior to his academic career, Rohde spent a decade as a public health microbiologist and molecular epidemiologist with the Texas Department of State Health Services Bureau of Laboratories and Zoonosis Control Division, and over 30 years researching rabies virus. While at the Department of Health Lab, Rohde worked on virus isolation using what he described as “old school” cell culture techniques, including immunoassays and hemagglutinin inhibition assays. He also identified different variants of rabies virus, using molecular biology techniques. Rohde spent time in the field shepherding oral vaccination programs that, according to passive surveillance methods have completely eliminated canine rabies in Texas. In the last 30-40 years, most rabies deaths in the U.S. have been caused by bats. Approximately 98% of the time rabies is transmitted through the saliva via a bite from a rabid animal. Post-exposure vaccination must take place before symptoms develop in order to be protective. Links for This Episode: Molecular epidemiology of rabies epizootics in Texas. Bat Rabies, Texas, 1996–2000. The Conversation: Rabies is an ancient, unpredictable and potentially fatal disease. Rohde and Charles Rupprecht, 2 rabies researchers, explain how to protect yourself. The One Health of Rabies: It’s Not Just for Animals. MTM listener survey!
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ASM's Young Ambassador, Aureliana Chambal, discusses the high incidence of tuberculosis in Mozambique and how improved surveillance can help block disease transmission in low resource settings.
Ashley's Biggest Takeaways: Mozambique is severely impacted by the TB epidemic, with one of the highest incidences in Africa (368 cases/ 100,000 people in the population). Human-adapted members of the Mycobacterium tuberculosis complex (MTBC) belong to 7 different phylogenetic lineages. These 7 lineages may vary in geographic distribution, and have varying impacts on infection and disease outcome. For decades, 2 reference strains have been used for TB lab research, H37Rv, which Chambal mentions, and Erdman. Both of these belong to TB Lineage 4. According to Chambal, the reference strains that we use for whole genome sequencing (worldwide) may be missing genes that are related the virulence (and/or resistance) of strains that are circulating in a given population and detected in clinical settings. Chambal is endeavoring to employ a new strain to control these analyses and better understand transmission dynamics in the community setting. Featured Quotes:The Schlumberger Foundation Faculty for the Future Fellowship is one of my proudest accomplishments for the 2023. I applied for this fellowship last year to pursue my Ph.D. It is a program that supports women coming from emerging and developing economies to pursue advanced research qualifications in science, technology, engineering and mathematics. I applied because I was looking to get more skills in microbiology, specifically tuberculosis, to pursue my Ph.D. at Nottingham Trent University.
Pathway to Microbiology ResearchMy trajectory is different because I have a bachelor’s in veterinary medicine. And during my undergrad, I always had more interest in the lab practice modules or disciplines. For the end of the [bachelor’s] project, I was looking to understand the anthelmintic effectiveness against the gastrointestinal parasites in goats. After I finished this project, I was looking to continue a related project, but unfortunately, I couldn't get work related to that..
Tuberculosis Genomic Diversity and Transmission Dynamics
In 2016, I applied for the National Institutes of Health of Mozambique, which is one of the biggest research institutions in my home country. That's when I was selected to work at the north region of Mozambique, specifically at the Nampula Tuberculosis Reference Laboratory. And then I moved to the public health laboratory as well, where I had the opportunity to work in the microbiology section. So, to be honest, my passion for microbiology started when I had the first contact with the TB lab, and then I couldn't separate myself from this area, tuberculosis.
In 2016, I had the opportunity to receive a mentorship. Our lab, the TB lab of Nampula, received mentorship from the American Society for Microbiology. And we worked with Dr. Shirematee Baboolal; she was the mentor of our lab. The main idea of the program was to get the lab accredited and to build technical capacity in the lab. And to be honest, at the time, I didn't have much experience in lab techniques to detect or diagnosis tuberculosis.
And I said to Dr. Shirematee, “I don't have much experience in this area, so, I don't know if I will be able to help you to accomplish these goals.” And she said, “If you want to learn, I can teach you, and you can be one of the best in this area.”
And then we started training with her. It was very interesting. The passion she passed to us about microbiology—and tuberculosis, in particular—was one of the triggers for my passion in this area. So, to be honest, Dr. Shirematee Baboolal was one of the persons that triggered my interest from tuberculosis. So, I have to say thank you to her!Mozambique is one of the higher burden countries of tuberculosis. So, our population is about 33 million people. And the case rate is high, it is approximately 360 per 100,000 people in the population, which is equivalent to over 110,000, which is equivalent 211,000 cases in the population. So, while I was working for the TB lab, I always had the desire to understand more about the transmission of the disease in the community.
Involvement with ASM Young Ambassador Program
And I felt like I didn't have enough skills to do that; I didn't the tools to do that. And I said, “Okay, let me try to look to improve the skills.” That's why for my master's degree I tried to understand the genomic diversity of M. tuberculosis and see how we can see the gene content diversity within the lineage for which is the most spread lineage worldwide, and is predominant in Mozambique. Afterwards, I tried to expand to the other lineages.
When I finished my master's degree, I felt that it was still missing something. I had the information about [TB] diversity, but I didn't get the point about transmission itself. That's why, when I went back and applied for my Ph.D., I structured my current project to specifically look at transmission and transmission clusters in the community.
I'm trying to see how we can expand the gold standard of whole genome sequencing to try to make it applicable for all settings, including the low resources settings where most TB cases happen.
So, M. tuberculosis itself doesn't have a lot of diversity between strains and within strains, because [strains] are very monomorphic. But you can find some genes that are different, specifically from the reference strain that we use, which is H37Rv. In the reference strain for M. tuberculosis, we saw is that many genes are missing—genes that are related to virulence. So, this information can be tricky, because it's the reference that we use worldwide to analyze our samples that come from whole genome sequencing. If we have genes missing, we are not [seeing] the complete information about the virulence of the bacterial strain that is circulating. So, my analysis was trying to understand how we can employ a new strain (that has at least most of the genes that are present in the other screens of the lineage) to control our analysis.
Whole genome sequencing requires a lot of computational resources. So, the main idea is to try to extend that pipeline to make applicable to use in all settings.
In Mozambique, we have whole genome sequencing equipment at the central level of the country, and the demand is high. But there is a queue for processing the samples. So, if we have a pipeline that [makes it so] anyone is able to analyze the data, we can have the results quick, and we can have more information for the public health sector.
And with transmission studies, you can have a clearer idea of where the recent infection happened. We can see how many cases we have and when the transmission started. And then we can [try to] track and block the transmission.So, I had the opportunity to hear about ASM’s Young Ambassador Program while I was working at the TB lab, in 2018. I spoke to Dr. Shirematee Baboolal and Dr. Maritza Urrego. And they told me about this position. Then, once I finished my masters [program], I applied for that position. I saw the requirements, and I felt like it was the right position for what I wanted to do for my community—to support the youth community and engage with my community back in Mozambique. I applied in 2020, and I got the position.
Links for the Episode: ASM Ambassador Program. ASM Global Public Health Program.
And I have to say, it is one of the best things I have done so far. Because since the implementation of this program in Mozambique, I have interacted with students in schools and universities. We have developed a lot of workshops. I feel like I can contribute scientifically to improve their lives, to improve their academic lives. And recently, we launched a program called Microbiology Kids Club. We go to schools, in church, and we teach children about science, specifically microbiology. We use cartoons and paint microbes to explain the importance of the microbes for the community for our daily activities. And it's very interesting how they are engaged. I can feel that it's a way to develop the taste for science in the children. So, I'm very happy with this accomplishment. In this role of young ambassador, I feel like I can contribute to my community back home.
I have so many ideas, so many dreams. I don't even know where to start! Because I have the ambitions to support my country back home. After I finish my Ph.D., I would like to create a robust technique that will help us to properly understand the [TB] transmission studies. So hopefully, with my Ph.D., I will be able to do that, or at least contribute something to support not only my country, but all low resources settings.
And I would also like to be like to support some public health policies that can help us. Because we don't have like a strong component that involves the lab, the public health sector—I feel like everything is separated. We need to combine everything if we want to fight against tuberculosis. So, my desire is also to create a link between all these specific sites so we can make our fight against TB stronger. I want to continue [to drive] awareness about the support we need in low resource settings to control the fight against tuberculosis. -
The scientific process has the power to deliver a better world and may be the most monumental human achievement. But when it is unethically performed or miscommunicated, it can cause confusion and division. Drs. Fang and Casadevall discuss what is good science, what is bad science and how to make it better.
Get the book! Thinking about Science: Good Science, Bad Science, and How to Make It Better
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Dr. James Morton discusses how the gut microbiome modulates brain development and function with specific emphasis on how the gut-brain axis points to functional architecture of autism.
Watch James' talk from ASM Microbe 2023: Using AI to Glean Insights From Microbiome Data https://youtu.be/hUQls359Spo
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Dr. Michael ginger, Dean of the School of Applied Sciences in the Department of Biological and geographical Science at the University of Huddersfield, in West Yorkshire, England discusses the atypical metabolism and evolutionary cell biology of parasitic and free-living protists, including Leishmania, Naegleria and even euglinids.
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Dr. Maria Eugenia Inda-Webb, Pew Postdoctoral Fellow working in the Synthetic Biology Center at MIT builds biosensors to diagnose and treat inflammatory disorders in the gut, like inflammatory bowel disease and celiac disease. She discusses how “wearables,” like diagnostic diapers and nursing pads could help monitor microbiome development to treat the diseases of tomorrow.
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Ashley's Biggest Takeaways Biosensors devices that engineer living organisms or biomolocules to detect and report the presence of certain biomarkers. The device consists of a bioreceptor (bacteria) and a reporter (fluorescent protein or light). Inda-Webb’s lab recently published a paper in Nature about using biosensors (Sub-1.4 cm3 capsule) to detect inflammatory biomarkers in the gut. The work is focused on diagnosing and treating inflammatory bowel disease, but Inda-Webb acknowledged that that is a large research umbrella. The next step for this research is to monitor the use of the biosensor in humans to determine what chemical concentrations are biologically relevant and to show that it is safe for humans to ingest the device. It is believed that the gut microbiome in humans develops in the first 1000 days to 3 years of life. Early dysbiosis in the gut has been linked to disease in adulthood. However, we do not have a good way to monitor (and/or influence) microbiome development. Inda-Webb hopes to use biosensors in diapers (wearables) to monitor microbiome development and prevent common diseases in adulthood. In 2015, Inda-Webb became ASM’s first Agar Art Contest winner for her piece, “Harvest System.” Inda-Webb is the 2023 winner of the ASM Award for Early Career Environmental Research, which recognizes an early career investigator with distinguished research achievements that have improved our understanding of microbes in the environment, including aquatic, terrestrial and atmospheric settings. Learn More About ASM’s Awards Program Featured Quotes:We engineer bacteria to sense particular molecules of interest—what we call biomarkers—if they are associated with a disease. And then, we engineer a way that the bacteria will produce some kind of molecule that we can measure—what we call reporter—so that could be a fluorescent protein or light, like the one that we have in this device.
Links for the Episode: Inda-Webb, et al. recent Nature publication: Sub-1.4 cm3 capsule for detecting labile inflammatory biomarkers in situ. Bacterial Biosensors: The Future of Analyte Detection.
The issue is that inflammation in the gut is really very difficult to track. There are no real current technologies to do that. That is like a black box. And so, most of what we measure is what comes out from the gut, and has its limitations. It doesn't really represent the chemical environment that you have inside, especially in areas where you're inflamed. So, we really needed technologies to be able to open a window in these areas.
The final device that I am actually bringing here is a little pill that the patient would swallow and get into the gut. And then they engineer bacteria that the biosensors, will detect, let's say, nitrous oxide, which is a very transient molecule. And the bacteria are engineered to respond to that in some way—to communicate with the electronics that will wirelessly transmit to your cell phone. And from there, to the gastroenterologist.
We make the bacteria produce light. If they sense nitrous oxide, they produce light, the electronics read that, and the [information] finally gets into your phone.
Part of the challenge was that we needed to make the electronics very very tiny to be able to fit inside the capsule. And also, the amount of bacteria that we use also is only one microliter. And so, imagine one microliter of bacteria producing a tiny amount of light. Finally, the electronics need to be able to read it. So that has been also part of the challenge.
In this case, you have 4 different channels. One is a reference, and then the other 3 are the molecule of your choice. So, for example, what we show in the paper here is that we can even follow a metabolic pathway. So, you can see one more molecule turn into the other one, then into the other one. I'm really excited about that. Because normally we kind of guess as things are happening, you know, but here you can see in real time how the different molecules are changing over time. I think that's pretty exciting for microbiologist.
The immediate application would be for a follow up. Let's say the patient is going to have a flare, and so you could predict it more much earlier. Or there's a particular treatment, and you want to see what is happening [inside the gut]. But for me, as a microbiologist, one of the things I'm most excited about will be more in the longer term.
One of my favorite experiments that I do with the students is the Winogradsky column, and everyone gets super excited. So, we all have nice feelings for that. And it’s basically a column where we asked the students to bring mud from a lake, for example, and then some sources of nutrients. And then, after 6months, you will see all the layers, which is super pretty—beautiful, nice colors. But actually, that gives the concept of how the microenvironment helps to define where, or how, bacteria build communities.
And so, what I think this device is going to do is to help us identify what is this microenvironment and to characterize that. And then, from there, to know if [an individual’s] microbiome is leaning towards the disease state, or if it's already in a serious or dangerous situation, to think about treatments that can lead to a more healthy state. So, I would just say it's really to have a window into the gut, and to be able to give personalized treatment for the patient.
So, one application: I was thinking, I'm from the Boston area. So, one problem we have is getting a tick bite, right? After that, you could actually have to go through a very traumatic, antibiotic regime. I would imagine, in that case, you could [use the biosensor to] get the baseline [measurement], and then if you need to take these antibiotics, the doctors can follow how your microbiome is responding to that. Because one of the problems is that antibiotics changed the oxidation level [in the gut], and that really affects a lot the microbiome. To that point, for example, I get to know patients that they were athletes, and then, after antibiotic treatment, they have serious problems with obesity. Their life gets really messed up in many ways.
And so, what I'm thinking is, if we could monitor earlier, there are a lot of ways that we could prevent that. We could give antioxidants; we could change the antibiotic. There are things that I think the doctor could be able to do and still do the treatment that we know.
And of course, [although] we talk a lot about how much trouble antibiotics are, for certain things, we still need [them].
[The multi-diagnostic diaper] is one of my pet projects. I really love it. So yeah, basically, the issue is that the microbiome develops in the first 3 years. People even say like, 1000 days, you know. But there's really no way to monitor that. And now we're seeing that actually, if the microbiome gets affected, there are a lot of diseases that you will see in adult life. So, if we will be able to monitor the microbiome development, I really believe that we'll be able to prevent many of the diseases of tomorrow.
What happens is that babies wear diapers. So, I thought it was really a very good overlap. We call that “wearables,” you know, like devices that you can wear, and then from there, measure something connected with health.
So, in the diaper, I was excited because—different from the challenge with the ingested device, which was so tiny—here, we don't have the limitation of space. So, we could measure maybe 1000 different biomarkers and see how that builds over time.
We can measure so many things. One could be just toxic elements that could be in the environment. I try to do very grounded science, and so, my question is always, ‘what’s the actionable thing to do?’ So, I'm thinking if there was a lot of toxicity, for example, in the carpet, or in the environment where you live, those are the easiest things to change, right?
Then also, other things connecting more with the metabolism. [Often] the parents don't know that the kid has metabolic issues. So, before that starts to build and bring disease, it would be best if you could detect it as early as possible. From there, with symbiotics, we are thinking there are a lot of therapies that could engineer bacteria to produce the enzymes that the kid can’t produce.
We could also [develop] other products, like for example, a t-shirt to measure the sweat. I'm also thinking more of the milk. I'm very excited about how the milk helps to build the microbiome in the right way. And that that's a huge, very exciting area for microbiologists. And so, we could also have nursing pads that also measure [whether] the mother has the right nutrients.
My family, my grandparents were farmers, and in Argentina, really the time for harvest is very important. You can see how the city and really the whole country gets very active. And at that time [during a course Inda-Webb was taking at Cold Spring Harbor] in this course, I could see that with yeast we were having a lot of tools that would allow us to be much more productive in the field. And I thought, ‘Oh, this feels like a harvest system for yeast.’ Yes. So that was how it [Inda-Webb’s winning agar artwork, ‘Harvest System’] came out.
I really love the people. Here, [at ASM Microbe 2023], I really found that how people are bringing so much energy and really wanted to engage and understand and just connect to this idea of human flourishing, right, giving value to something, and saying, ‘okay, we can actually push the limits of what we know.’ How beautiful is that? And you know, we can learn from that. That was very exciting.
ASM Agar Art Contest
Have you ever seen art created in a petri dish using living, growing microorganisms? That's agar art! ASM's annual Agar Art Contest is a chance for you to use science to show off your creative skills.
Submissions Are Now Being Accepted!
This year's contest theme is "Microbiology in Space." Head over to our Contest Details page to get all of the information about what you need to submit your entry. Submissions will be accepted until Oct. 28!
Let us know what you thought about this episode by tweeting at us @ASMicrobiology or leaving a comment on facebook.com/asmfan. -
Dr. Gary Procop, CEO of the American Board of pathology and professor of pathology at the Cleveland Clinic, Lerner School of Medicine discusses the importance of early detection and diagnosis in order to prevent fungal invasion leading to poor outcomes, particularly in immunocompromised patients. He emphasizes the importance of thinking fungus early, shares his passion for mentoring and talks about key updates in the recently released 7th Edition of Larone’s Medically Important Fungi.
Ashley's Biggest Takeaways Many invasive fungal infections are angiotrophic, meaning they actually grow toward, and into, blood vessels. Once the fungus has penetrated the blood vessel, the blood essentially clots, causing tissue downstream from the blood clot to die (infarction). When tissues that have been excised are viewed under the microscope, hyphal elements can be seen streaming toward or invading through the wall of the blood vessels. Once the clot forms, those hyphal elements can be seen in the center of the blood vessel where only blood should be. Antifungals cannot be delivered to areas where the blood supply has stopped. Therefore, treatment requires a combined surgical and medical approach, and the process is very invasive. Early detection can prevent these bad outcomes by allowing antifungal treatment to be administered before angioinvasion occurs. Links for the Episode: Expand your clinical mycology knowledge with the recently released 7th edition of Larone's Medically Important Fungi: A Guide to Identification. Written by a new team of authors, Lars F. Westblade, Eileen M. Burd, Shawn R. Lockhart and Gary W. Procop, this updated edition continues the legacy of excellence established by founding author, Davise H. Larone.
Since its first edition, this seminal text has been treasured by clinicians and medical laboratory scientists worldwide. The 7th edition carries forward the longstanding tradition of providing high-quality content to educate and support the identification of more than 150 of the most encountered fungi in clinical mycology laboratories.
Get your copy today with $1 flat rate shipping within the U.S. or order the e-book! ASM members enjoy 20% off at checkout using the member promo code.Let us know what you thought about this episode by tweeting at us @ASMicrobiology or leaving a comment on facebook.com/asmfan.
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From antifungal resistance to disaster microbiology and tales of visible mold growing across the skin of patients following a tornado in Joplin, Missouri, Dr. Shawn Lockhart, Senior Clinical Laboratory Advisor in the Mycotic Diseases Branch at the CDC talks all things fungi—complete with references to pop TV shows and the recently released 7th Edition of Larone’s Medically Important Fungi.
Links mentioned:
Larone's Medically Important Fungi: A Guide to Identification, 7th Edition (Use code: MCR20 at checkout for 20% off) CDC’s Mycotic Diseases Branch conducts an annual training course on the identification of pathogenic molds. -
Dr. Kate Howell, Associate Professor of Food Chemistry at the University of Melbourne, Australia discusses how microbes impact the flavor and aroma of food and beverages and shares how microbial interactions can be used to enhance nutritional properties of food and beverage sources. Ashley's Biggest Takeaways Saccharomyces means sugar-loving fungus. Humans have similar olfactory structures and mechanisms as insects and are similarly attracted to fermenting or rotting fruits produced by Saccharomyces. Research has shown that insects (and humans) prefer yeasts that produce more esters and aromatic compounds. Palm wine is a product that is made from sap collected from palm trees (palm sap) across the tropical band of the world. Fruity flavors appear to be less important to persistence of Saccharomyces strains in an Indonesian palm wine fermentation. This may be because palm wine fermentation is very quick, generally 1-3 days often, with a maximum of 5 days for fermentation to be conducted. Wineries, on the other hand, ferment annually (one fermentation per year/vintage), when the grapes are right. Grape wine fermentations can take 7 days to 2 weeks to complete. So different selections likely take place between the 2 fermentation products. Featured Quotes:
When we start drawing our lens on how microbes produce food for humans, we're coopting a process that happens quite naturally. Here I'll start off talking about Saccharomyces cerevisiae, the main fermenting yeast in food and beverage production, because it's one of the most studied organisms and was the first eukaryote to be sequenced.
Links for the Episode: LC-ESI-QTOF/MS Characterisation of Phenolic Acids and Flavonoids in Polyphenol-Rich Fruits and Vegetables and Their Potential Antioxidant Activities. Frozen, canned or fermented: when you can't shop often for fresh vegetables, what are the best alternatives? Early Prediction of Shiraz Wine Quality Based on Small Volatile Compounds in Grapes. Building the climate resilience of Melbourne's Food System.
Saccharomyces cerevisiae, as the name implies, loves sugar, and it flourishes when there's a lot of sugar in the environment. Where is sugar found? In fruits, and that's done quite deliberately, because fruits develop sugars and flavors and aromas to attract a birds or insects or anything else that can carry their seeds elsewhere for dispersal.
Now, Saccharomyces lies dormant in the environment in a spore before it encounters a sugar-loving environment. And then it replicates very quickly and tends to dominate fermentation. Humans have coopted that into our kitchens, into our meals, into our lives, and we use that process to produce food.
As Saccharomyces starts to use this sugar, it balances up its metabolism. And as it does this, it produces aromas. These aromas have a lot of important characteristics. Humans love them, but insects also love them too.
I've been interested in the yeasts that are found naturally in sourdough starters. Sourdough is a really interesting system. Because you've got yeast and bacteria interacting with one another.
One of the things we are collaborating on with colleagues in France at Inrae, Dr. Delphine Sicard, is to understand some of the non-Saccharomyces yeasts that are naturally occurring in sourdough starters. So here we're looking at a collection of a yeast called Kazachstania humilis and trying to understand how it has adapted to the sourdough environment, how its sustained over time and how different global populations differ to one another.
And this, of course, is of interest to the baking industry because not only do artisanal bakers have sort of an undiscovered wealth of biodiversity in their starters, baking companies also have an interest in using different sorts of flavors and bread for the commercial markets.
The connection between a chemical profile and a person’s sensory preference isn't something that's complete and direct. So, in every method that we use, there's always caveats, but we try to correlate it. Let's start off with the chemical characterization. We use headspace sampling, analytical chemistry, separation with gas chromatography and identification with mass spectrometry.
And we use different 2-dimensional methods to be able to understand what the very small compounds are, and to be able to identify them. We can semi-quantify these to be able to make comparisons between different fermentations.
We know from wine fermentations and understanding preferences of wine that, in some cases, a particular increase, or an abundance of a particular compound, can be extremely attractive. And that might depend on the style of wine.
What we've discovered through this process is that different people prefer different flavors. Makes sense, doesn't it? We like different things. But some really interesting results from our lab, show that people from different cultural backgrounds have different preferences. And here we're using here in Melbourne, I'm very lucky to work with some very talented postdocs and Ph.D. students from China, who have very different preferences for wine than an Australian does. Of course, Australians are quite heterogeneous in their in their cultural diversity as well. But there's certain flavors that our Chinese colleagues tend to prefer. So we decided to investigate this a little bit more.
So for this study, we recruited wine experts from Australia, actively working in the wine industry, and also wine experts from China, working in the wine industry, and brought them to campus and ask them to rate their preferences on particular aromas and flavor characteristics that they noted in a panel of wines. These were very high-quality wines. We knew with wine experts, we couldn't just give them our loved wines, for example, which can be a little bit patchy quality wise. We asked them to rate their preferences, and then we collected saliva samples.
The saliva samples were really interesting. We looked at 2 different aspects. We looked at the proteins that were present in the saliva samples. And we also looked at the oral microbiome. So the salivary microbiome—the bacteria, in particular—that are present. We found some really interesting things. And this has sparked a big area in our lab.
So while the main enzymatic activities in the different groups of participants were quite similar—so esterase activity, Alpha amylase activity were similar—we found that there was a difference in the abundance of proline rich proteins and other potential flavor carrying compounds. Now, this is quite speculative. We'd like to know why this is the case. And so we're delving a little bit further into this area.
What we do know though is that the abundances, especially if these proline rich proteins, is correlated with how people perceive the stringency. Now stringency is one of those characteristics in wine which is quite difficult to appreciate. It’s a lack of drying characteristic on the tongue and in the mouth and oral cavity. Some people find it quite attractive, others don't.
But we found that the abundance of these polyproline-rich proteins correlates with stringency. This is, in fact, found in other studies because proline-rich proteins interact with polyphenols in the wine, and precipitate, which changes the sensation of astringency in the oral cavity. So here we've got a nice link to protein abundance and how people perceive flavor. But we're talking about microbiology, so maybe I should delve into the microbiological aspects of these studies as well.
In that particular study that I'm referring to, we used wines that were naturally fermented, and that's the other variability that we need to consider when we think about wines from different areas. So, a natural fermentation, in a wine sense, is the grapes are harvested, and whatever microflora is present on the grapes will just ferment, and we often don't know what the main fermenting parties are. But if you contrast that with a majority of commercial wine that's produced, mainly in Australia, but also worldwide, it's inoculated with a selected strain of Saccharomyces or maybe 2 selected strains of Saccharomyces, and that tends to produce a fairly similar flavor profile, regardless of region.
So, you can flatten out geographical characteristics and indications of flavor by inoculating a particular strain of yeast to ferment. That's not true with a natural fermentation, because that's conducted by the yeasts, and also the bacteria which just happened to be in the environment. So, I agree with you there is a lot of regional variation with wine flavor. And we can correlate that with regional diversity of yeast, but only if the wines are naturally fermented not if they're inoculated with a selected strain.
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Dr. Steve Diggle, ASM Distinguished Lecturer and Microbiology Professor at the Georgia Institute of Technology in Atlanta, Georgia and Dr. Freya Harrison, Associate Microbiology Professor at the University of Warwick in Coventry, U.K., discuss the science behind medieval medical treatments and the benefits of interdisciplinary research.
Ashley's Biggest Takeaways Diggle and Harrison met in Oxford, where Harrison was finishing up her Ph.D. and Diggle was doing background research for his work studying evolutionary questions about quorum sensing. When Diggle began searching for a postdoc, Harrison, who had been conducting an independent fellowship at Oxford and studying social evolution, applied. The AncientBiotics Consortium is a group of experts from the sciences, arts and humanities, who are digging through medieval medical books in hopes of finding ancient solutions to today’s growing threat of antibiotic resistance. The group’s first undertaking was recreation and investigation of the antimicrobial properties of an ancient eyesalve described in Bald’s Leechbook, one of the earliest known medical textbooks, which contains recipes for medications, salves and treatments. The consortium found that the eyesalve was capable of killing MRSA, a discovery that generated a lot of media attention and sparked expanded research efforts. The group brought data scientists and mathematicians into the consortium (work driven by Dr. Erin Connelly from the University of Warwick). Together, the researchers began scouring early modern and medieval texts and turning them into databases. The goal? To mathematically data mine these recipes see which ingredients were very often or non-randomly combined in ancient medical remedies. The group recently published work showing synergistic antimicrobial effects of acetic acid and honey. They are also working to pull out the active compounds from Bald’s eyesalve and make a synthetic cocktail that could be added to a wound dressings. A 1,000-Year-Old Antimicrobial Remedy with Antistaphylococcal Activity. Medieval medicine: the return to maggots and leeches to treat ailments. A case study of the Ancientbiotics collaboration. Phase 1 safety trial of a natural product cocktail with antibacterial activity in human volunteers. Sweet and sour synergy: exploring the antibacterial and antibiofilm activity of acetic acid and vinegar combined with medical-grade honeys.
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Dr. Jessica Lee, scientist for the Space Biosciences Research Branch at NASA’s AIMS Research Center in Silicon Valley uses both wet-lab experimentation and computational modeling to understand what microbes really experience when they come to space with humans. She discusses space microbiology, food safety and microbial food production in space and the impacts of microgravity and extreme radiation when sending Saccharomyces cerevisiae to the moon. Ashley's Biggest Takeaways Lee applied for her job at NASA in 2020. Prior to her current position, she completed 2 postdocs and spent time researching how microbes respond to stress at a population level and understanding diversity in microbial populations. She has a background in microbial ecology, evolution and bioinformatics. Model organisms are favored for space research because they reduce risk, maximize the science return and organisms that are well understood are more easily funded. Unsurprisingly, most space research does not actually take place in space, because it is difficult to experiment in space. Which means space conditions must be replicated on Earth. This may be accomplished using creative experimental designs in the wet-lab, as well as using computational modeling. Links for the Episode: Out of This World: Microbes in Space. Register for ASM Microbe 2023. Add “The Math of Microbes: Computational and Mathematical Modeling of Microbial Systems,” to your ASM Microbe agenda.
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